Physical Sciences Inc. proposes to develop a new, integrated multimodal adaptive optics small animal imager, including AO-OCT and AO scanning laser fluorescence (fAOSLO), and to demonstrate its applications to detecting pathology in the retinas of rodent models of eye disease. The imaging platform includes novel design elements such as adaptable wavefront sensing methods enabling dynamic and static AO correction in selected layers; integrated Badal optometer system with path-length-locked OCT reference arm for flexible AO-OCT-guided imaging, and co-scanning AO-OCT/fAOSLO rasters for enhanced fluorescence sensitivity and co-registration in anesthetized rodents. Together with collaborators at Children's Hospital Boston (CHB), we propose to demonstrate the imaging platform in a GFP mouse (B6.129P-Cx3cr1tm1Litt/J mice) model of STZ-induced diabetic retinopathy. The rapidly growing array of small animal models of human eye disease has significantly increased the need for new in vivo animal fundus imaging modalities with cellular resolution. However, there are currently no commercial AO platforms for high resolution in vivo imaging which can exploit such features. A successful Phase I program will result in a multimodal adaptive optics small animal imaging (MAOSI) platform with simultaneous AO- OCT, fAOSLO, and improved AO control for 3D structural and functional imaging. Such a device has immediate research and drug discovery applications and markets.